This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Broadly defined, social cognition is a collection of abilities which are important for interpreting and interacting with our social environment. However, despite many studies identifying key brain structures, the connection between microanatomy and social cognition remains very much obscure. Some particularly interesting evidence in the field has come from the study of Williams Syndrome (WS). WS is a rare genetic and neurodevelopmental condition with particular cognitive deficits but also a characteristic behavioral profile that includes an increase in affect and sociability. Neuroimaging findings have indicated that the affiliative behavior in WS is related to enhanced development of anterior regions of the brain (including parts of the frontal and temporal lobes). Despite the importance of these implications, research in this area has been limited, in part, due to the scarcity of WS brain tissue. Utilizing the largest collection of postmortem WS tissue, we are able for the first time to study the underlying neuronal differences in WS and typical developing (TD) brain tissue. Specifically, we propose to investigate: (1) differences in distribution of elemental factors associated with synaptic activity and cellular metabolism (2) how these differences relate to the differences in the neuronal number and cell body size that contribute to observed changes in density, (3) and the differences in connectivity inferred by 3D architecture of neurons within cortical layers. The areas targeted are the posterior orbital and ventromedial prefrontal cortex;anterior cingulate, frontoinsular cortex, frontal pole, hippocampus and the amygdala. The project will thus provide unprecedented insights into the microcircuitry of the social brain.